放射治疗（RT）是消灭原发肿瘤的重要策略，也可能诱发Abocopal效应。人类血清白蛋白（HSA）纳米粒子（NP）被用于控制释放顺铂，以降低顺铂的系统毒性，并添加金（Au）以增强RT诱导的免疫原性细胞死亡，并增强Abocopal 抗肿瘤免疫。设计的基于白蛋白的顺铂共轭AuNPs与放射性治疗同时施行。用放射性治疗（每分12Gy进行2分治疗，总量24Gy），顺铂或Au-顺铂NP处理移植有同源性BALB/c小鼠Lewis肺癌（LLC）或小鼠MB49肿瘤模型的C57BL/6小鼠。将放射性治疗与顺铂或Au-顺铂NP相结合，既能有效地摧毁原发肿瘤，又能诱导免疫原性细胞死亡（ICD），释放危险相关的分子模式。这增强了效应器肿瘤浸润免疫细胞（TIIs）的招募，包括NKT细胞和CD8 + T细胞，并激发了更高比例的专业抗原呈递细胞（APCs）CD11c + 树突状细胞。观察到暂时的体重下降，伴随着肝毒性、肾毒性和造血抑制，这是针对顺铂而不是Au-顺铂NP组的系统不良事件。当与放射性治疗结合使用时，顺铂和Au-顺铂NP都表现出相同的减少转移潜力的能力，经过抑制未照射的侧翼肿瘤生长和减少转移性肺肿瘤负担的确认，这有助于生存状况的改善。在放射性治疗与顺铂或Au-顺铂NP的配合下，仍能观察到效应器TIIs包括CD8 + T细胞和树突状细胞在远程肺肿瘤微环境中的移动和丰度，证明其抗肿瘤免疫治疗活性得到进一步提高。与顺铂相比，基于白蛋白的Au-顺铂NP表现出类似但没有优越的抗肿瘤免疫治疗活性，同时减少系统不良事件，并可与放射性治疗同时施行。可以设计替代性纳米粒子配方以进一步改善抗癌效果。版权所有©2023年。由Elsevier Inc.发表。

Ablative radiotherapy (RT) is an important strategy to eliminate primary tumor and can potentially induce the abscopal effect. Human serum albumin (HSA) nanoparticle (NP) was used for controlled release of cisplatin to decrease cisplatin's systemic toxicity, and gold (Au) was added to increase RT-induced immunogenic cell death and potentiate the abscopal antitumor immunity.The designed albumin-based cisplatin-conjugated AuNPs were administered concurrently with ablative RT. C57BL/6 mice implanted with syngeneic murine Lewis lung carcinoma (LLC) or murine MB49 tumor models were treated with ablative RT (12 Gy per fraction for 2 fractions, total 24 Gy), cisplatin, or Au-cisplatin NPs.Combining ablative RT with cisplatin or Au-cisplatin NPs both destroyed the primary tumor effectively and elicited immunogenic cell death (ICD) accompanied by release of danger-associated molecular patterns. This enhanced recruitment of effector tumor-infiltrating immune cells (TIIs), including NKT cells and CD8+ T cells, and elicited an increased percentage of professional antigen-presenting cells (APCs) CD11c+ dendritic cells. Transient weight loss, accompanying hepatotoxicity, nephrotoxicity, and hematopoietic suppression, was observed as a systemic adverse event in the cisplatin but not the Au-cisplatin NPs group. Cisplatin and Au-cisplatin NPs both showed equivalent ability to reduce metastatic potential when combined with ablative RT, confirmed by suppressed un-irradiated flank tumor growth and decreased metastatic lung tumor burden, which translated to improved survival. Mobilization and abundance of effector TIIs including CD8+ T cells and dendritic cells were observed in the distant lung tumor microenvironment after ablative RT with cisplatin or Au-cisplatin NPs, demonstrating increased antitumor immunotherapeutic activity as an abscopal effect.Compared to cisplatin, the albumin-based Au-cisplatin NPs exhibited equivalent but no superior antitumor immunotherapeutic activity while reducing systemic adverse events, and can be safely administered concurrently with ablative RT. Alternative nanoparticle formulations may be designed to further improve anticancer outcomes.Copyright © 2023. Published by Elsevier Inc.